NPASS Compound

Structure

CID12124 OpenBabel06191715342D 26 29 0 0 1 0 0 0 0 0999 V2000 4.1366 1.0375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 4.9039 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0776 2.8695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4461 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7341 -0.4178 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4307 2.7499 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1691 2.0874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.6704 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4461 3.3398 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8772 1.9650 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7120 2.0882 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5463 2.5678 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 3.3398 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2687 1.2978 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7230 2.0874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4461 0.8351 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 0.8351 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4461 1.6704 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7120 3.0882 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.8976 4.1218 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8791 3.1764 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4507 0.4133 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7747 1.8648 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4515 4.1218 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6261 2.0874 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 24 1 0 0 0 0 2 25 1 0 0 0 0 3 26 1 0 0 0 0 4 5 1 0 0 0 0 4 16 1 0 0 0 0 5 20 1 0 0 0 0 6 10 2 0 0 0 0 6 12 1 0 0 0 0 7 9 1 0 0 0 0 7 16 1 0 0 0 0 8 11 1 0 0 0 0 9 13 1 0 0 0 0 9 21 2 0 0 0 0 10 14 1 0 0 0 0 10 24 1 0 0 0 0 11 18 1 6 0 0 0 11 19 1 0 0 0 0 12 18 1 0 0 0 0 12 22 2 0 0 0 0 13 15 2 0 0 0 0 13 25 1 0 0 0 0 14 18 1 6 0 0 0 14 23 1 0 0 0 0 15 17 1 0 0 0 0 15 26 1 0 0 0 0 16 17 1 6 0 0 0 17 8 1 1 0 0 0 17 20 1 0 0 0 0 18 16 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	383.11
Volume:	354.062
LogP:	0.678
LogD:	0.365
LogS:	-2.249
# Rotatable Bonds:	3
TPSA:	90.93
# H-Bond Aceptor:	7
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.567
Synthetic Accessibility Score:	5.801
Fsp3:	0.722
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.779
MDCK Permeability:	4.4808315578848124e-05
Pgp-inhibitor:	0.003
Pgp-substrate:	0.986
Human Intestinal Absorption (HIA):	0.013
20% Bioavailability (F20%):	0.237
30% Bioavailability (F30%):	0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.849
Plasma Protein Binding (PPB):	30.91215705871582%
Volume Distribution (VD):	1.16
Pgp-substrate:	73.67778778076172%

ADMET: Metabolism

CYP1A2-inhibitor:	0.008
CYP1A2-substrate:	0.988
CYP2C19-inhibitor:	0.018
CYP2C19-substrate:	0.79
CYP2C9-inhibitor:	0.003
CYP2C9-substrate:	0.048
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.128
CYP3A4-inhibitor:	0.095
CYP3A4-substrate:	0.937

ADMET: Excretion

Clearance (CL):	5.427
Half-life (T1/2):	0.277

ADMET: Toxicity

hERG Blockers:	0.008
Human Hepatotoxicity (H-HT):	0.742
Drug-inuced Liver Injury (DILI):	0.386
AMES Toxicity:	0.571
Rat Oral Acute Toxicity:	0.918
Maximum Recommended Daily Dose:	0.926
Skin Sensitization:	0.45
Carcinogencity:	0.992
Eye Corrosion:	0.064
Eye Irritation:	0.015
Respiratory Toxicity:	0.989

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC12124

Natural Product ID:	NPC12124
*Common Name:**	Dauricumidine
IUPAC Name:	n.a.
Synonyms:	Dauricumidine
Standard InCHIKey:	SBALNGLYQFMKPR-MOSHLBJQSA-N
Standard InCHI:	InChI=1S/C18H22ClNO6/c1-24-10-6-12(22)18(14(10)23)11(19)8-17-15(26-3)13(25-2)9(21)7-16(17,18)4-5-20-17/h6,11,14,20,23H,4-5,7-8H2,1-3H3/t11-,14-,16+,17+,18+/m0/s1
SMILES:	COC1=CC(=O)[C@]2([C@H](C[C@@]34C(=C(C(=O)C[C@@]23CCN4)OC)OC)Cl)[C@H]1O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL237765
PubChem CID:	10000052
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002791] Acutumine and related alkaloids

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO20751	Hypserpa nitida	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17723297]
NPO20751	Hypserpa nitida	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	2
Others	3

Activity Type	# Activity
NON-MOLECULAR	1
Organism	2
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	CC50	=	1859000.0	nM	PMID[530597]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	450000.0	nM	PMID[530597]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	>	3854000.0	nM	PMID[530597]
NPT2	Others	Unspecified		Ratio CC50/IC50	=	4.13	n.a.	PMID[530597]
NPT2	Others	Unspecified		Ratio CC50/IC50	<	1.0	n.a.	PMID[530597]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC12124 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	168
0.1-0.2	1190
0.2-0.3	8060
0.3-0.4	23514
0.4-0.5	9036
0.5-0.6	708
0.6-0.7	14
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC44200
0.9571	High Similarity	NPC15440
0.9571	High Similarity	NPC264958
0.9571	High Similarity	NPC185590
0.8897	High Similarity	NPC266697
0.8857	High Similarity	NPC45813
0.6474	Remote Similarity	NPC470539
0.6452	Remote Similarity	NPC476951
0.6169	Remote Similarity	NPC88190
0.6144	Remote Similarity	NPC476952
0.6125	Remote Similarity	NPC215507
0.6	Remote Similarity	NPC35037
0.5965	Remote Similarity	NPC201899
0.5965	Remote Similarity	NPC471674
0.5839	Remote Similarity	NPC96010
0.5839	Remote Similarity	NPC317654
0.5833	Remote Similarity	NPC473955
0.5833	Remote Similarity	NPC235625
0.5828	Remote Similarity	NPC478139
0.5823	Remote Similarity	NPC23963
0.5817	Remote Similarity	NPC469466
0.5793	Remote Similarity	NPC315011
0.5789	Remote Similarity	NPC473232
0.5776	Remote Similarity	NPC474371
0.5732	Remote Similarity	NPC201889
0.5732	Remote Similarity	NPC96731
0.5732	Remote Similarity	NPC106791
0.5714	Remote Similarity	NPC204639
0.5669	Remote Similarity	NPC147707
0.566	Remote Similarity	NPC230849
0.566	Remote Similarity	NPC11379
0.5658	Remote Similarity	NPC470535
0.5652	Remote Similarity	NPC280498
0.5647	Remote Similarity	NPC88943
0.564	Remote Similarity	NPC803
0.5638	Remote Similarity	NPC251884
0.5638	Remote Similarity	NPC70369
0.5633	Remote Similarity	NPC471673
0.5625	Remote Similarity	NPC238323
0.5621	Remote Similarity	NPC470536
0.5621	Remote Similarity	NPC230889
0.5621	Remote Similarity	NPC474725
0.5618	Remote Similarity	NPC315809
0.5618	Remote Similarity	NPC314050
0.561	Remote Similarity	NPC471086

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC12124 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	107
0.1-0.2	886
0.2-0.3	3975
0.3-0.4	3449
0.4-0.5	692
0.5-0.6	41
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5793	Remote Similarity	NPD2101	Approved
0.568	Remote Similarity	NPD6333	Approved
0.568	Remote Similarity	NPD6334	Approved
0.5663	Remote Similarity	NPD6845	Suspended
0.5636	Remote Similarity	NPD6914	Discontinued
0.561	Remote Similarity	NPD6033	Approved

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data